The promise vs. the payoff of the NIH intramural program

‘In these times of tremendous scientific opportunities and highly constrained budgets, the relative value of these investments must be examined carefully’

By Jeremy Berg

Most researchers probably think of the National Institutes of Health as primarily a grant-making agency. However, the NIH also directly supports research on its campuses as part of the Intramural Research Program.

The IRP mission statement asserts that the IRP should “conduct distinct, high-impact laboratory, clinical, and population-based research” and that it should support research that “cannot be readily funded or accomplished in traditional academia.”

This is a noble aspiration. However, while the NIH’s budget is shrinking, the IRP’s share of it is growing, which means that other components of the NIH portfolio are being sacrificed, including extramural investigator-initiated basic research.

Growth of intramural activities

In 2003, when I became an NIH institute director, the overall NIH appropriation was $26.74 billion, while the overall intramural program consumed $2.56 billion, or 9.6 percent. In fiscal 2013, the overall NIH appropriation was $29.15 billion, and the intramural share had grown to $3.26 billion, or 11.2 percent.

Some of this growth is because of ongoing intramural activities, such as those involving the NIH Clinical Center, where, like at other hospitals, costs are very hard to contain below rates of inflation, or because of new activities, such as the NIH Chemical Genomics Center. The IRP is particularly expensive in terms of taxpayer dollars, because it is difficult to leverage the federal support to the IRP with funds from other sources as occurs in the extramural community.

Individual investigators within the IRP have, no doubt, been feeling the pinch of budgets that do not keep up with the increased costs of doing biomedical research. Nonetheless, in these times of tremendous scientific opportunities and highly constrained budgets, the relative value of these investments must be examined carefully.

What we do know

Funding for investigators within the IRP can be examined through the NIH RePORTER site by searching for projects with the activity code ZIA. For fiscal 2013, this search yielded 2,788 awards totaling $1.93 billion, with a median size of $514,000 total costs for the year. The effective average indirect rate for the IRP is not reported, to my knowledge, so it is not straightforward to convert this into direct costs. But even at an indirect cost rate of 100 percent, this is larger than an average extramural grant.

One IRP principal investigator can have multiple ZIA awards, and the separation of funds into different awards is largely at the discretion of the PI (based on how distinct different projects are). These awards can be aggregated into total funding for each of the 1,207 PIs to yield the distribution shown in the figure.

At the very high end (budgets of more than $5 million) are investigators who run large multi-investigator programs, such the National Institute of Allergy and Infectious Diseases Vaccine Development Center (with a 2013 budget of $12.7 million). Some individual investigators also appear to be very well funded, such as NIH Director Francis S. Collins, for whom NIH RePORTER lists three projects totaling $4.24 million. The median for all 1,207 PIs is $1.27 million.

‘Much should be expected of IRP investigators’

Boards of Scientific Counselors typically review the scientific plans and progress of IRP investigators every four years. These BSCs serve a role analogous to study sections in the extramural program, evaluating progress and plans for upcoming projects.

The reviews are relatively heavily weighted toward past accomplishments as a predictor of future achievements. This approach to evaluation has many benefits, potentially allowing IRP investigators to take on long-term or risky projects or to change directions relatively nimbly.

With these levels of support and this relatively flexible review system, much should be expected of IRP investigators.

Through the use of publicly available tools, such as those noted in my column last month about NIH Pioneer awardees and Howard Hughes Medical Institute investigators, it should be possible to evaluate in at least semiquantitative terms how the discoveries and other outputs from IRP investigators compare with those from other groups.

Giving credit where credit is due

The IRP sports some tremendous accomplishments as part of both its long-term and recent history. The accomplishments made within the IRP fall into several categories.

The first involves fundamental discoveries made by individual investigators. An archetypal example that should be familiar to American Society for Biochemistry and Molecular Biology members is Christian Anfinsen’s studies of protein folding, including the Nobel Prize-winning discovery that reduced, denatured ribonuclease A spontaneously refolds to produce active enzyme in high yield, indicating that the amino-acid sequence of a protein encodes its three-dimensional structure.

The second category involves longer-term research projects that would have been very challenging to support in most other settings. A key example is the development of macromolecular structure determination by nuclear magnetic resonance methods. In this arena, IRP researchers contributed, along with those in European laboratories, to the birth and development of this important and still developing approach.

The third involves both basic and clinical research related to humans and human tissues. Two factors helped drive IRP research in this field, the so-called “doctor draft” and the NIH Clinical Center. The “doctor draft” encouraged many talented young physicians to train within the IRP, particularly during the period of the Vietnam War, while the NIH Clinical Center is a unique institution for conducting clinical research, particularly for rare or emerging diseases.

The final area involves activities that serve the national and international scientific community, represented by the National Center for Biotechnology Information, which houses important databases such as PubMed, GenBank and PubChem. The NCBI averages 45 million pageviews from 3.7 million unique users per day with a peak Web hit rate of 7,000 hits per second. It is hard to overestimate how great an impact the evolving tools available through NCBI have had on biomedical science.

Congress urges ‘extra level of scrutiny’

Interestingly, the report language that accompanies the recently passed omnibus appropriations bill includes the recommendation that the “extra level of scrutiny” being applied recently to well-funded extramural investigators “apply equally in intramural investigators as well.”

I have written previously in support of extra scrutiny for well-funded investigators. It is important to note that I do not favor a hard cap but rather a process so that the output of well-funded investigators is examined in the context of their level of funding when funding decisions are made. This should help ensure that scarce federal resources are distributed in a manner that promotes the most productive and robust biomedical research system. I welcome your thoughts on how best to achieve this essential goal.

Jeremy Berg (jberg@pitt.edu) is the associate senior vice-chancellor for science strategy and planning in the health sciences and a professor in the computational and systems biology department at the University of Pittsburgh.